High performance fluorescent optical sensor

ABSTRACT

An optical sensor device for determining the presence or concentration of an analyte, contains a waveguide disposed over a light source and a light detector mounted on a surface of a substrate and separated by an internal baffle, wherein the waveguide has a thickness corresponding to a far field emission point of the light source as determined by a light shielding baffle between the light source and light detector. An analyte indicator matrix is disposed on the outer surface of the waveguide. The sensor device geometry takes advantage of only direct illumination of the indicator matrix, and direct collection of indicator matrix illumination, without any significant reflection by said waveguide. Undesirable light noise generated by the light source passes directly out of the device through the waveguide.

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority under 35 U.S.C. §119(e) toProvisional Application Serial No. 60/338,647 filed Dec. 11, 2001.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] This invention relates generally to sensor devices for detectionof electromagnetic emissions from an indicator having an analyte ofinterest permeating therethrough, wherein the characteristics of theemissions vary as a function of the concentration of the analyte. Moreparticularly, the invention relates to improvements in the design andperformance of such sensor devices.

[0004] 2. Background Art

[0005] U.S. Pat. No. 5,517,313, the disclosure of which is incorporatedherein by reference, describes a fluorescence sensing device comprisinga layered array of a fluorescent indicator molecule-containing matrix(hereafter “fluorescent matrix”), a high-pass filter and aphotodetector. In this device, a light source, preferably alight-emitting diode (“LED”), is located at least partially within theindicator material, such that incident light from the light sourcecauses the indicator molecules to fluoresce. The high-pass filter allowsemitted light from the indicator molecules to reach the photodetector,while filtering out scattered incident light from the light source. Ananalyte is allowed to permeate the fluorescent matrix, changing thefluorescent properties of the indicator material in proportion to theamount of analyte present. The fluorescent emission is then detected andmeasured by the photodetector, thus providing a measure of the amount orconcentration of analyte present within the environment of interest.

[0006] One advantageous application of a sensor device of the typedisclosed in the '313 patent is to implant the device in the body,either subcutaneously or intravenously or otherwise, to allowinstantaneous measurements of analytes to be taken at any desired time.For example, it is desirable to measure the concentration of oxygen inthe blood of patients under anesthesia, or of glucose in the blood ofdiabetic patients.

[0007] Since the invention of the device described in the '313 patent,the present inventors have developed a number of design improvementswhich have significantly enhanced the performance, reliability andlongevity of optical sensor devices of the type described in the '313patent.

[0008] In particular, because of the size and weight restrictions placedon such sensor devices especially for in-vivo or in-situ applications,it is important to maximize the efficiency of the available indicatormatrix in order to obtain a more reliable and accurate measurementsignal, while minimizing power consumption and heat generation.Additionally, the sensor device design should permit cost-effective highvolume manufacturing at a reasonable selling price. Further, maximizingthe longevity of the device is desirable especially where the devicemust be implanted in the body for in-situ detection of bioanalytes.

SUMMARY OF THE INVENTION

[0009] In accordance with an aspect of the present invention, an opticalsensor device for determining the presence or concentration of ananalyte, is provided, including a substrate; a light-shielding bafflelayer formed on the substrate, and containing at least two cavitiestherein; a light source for emitting light primarily of a preselectedwavelength upon energization, mounted on a surface of the substrate inone of the cavities; a light detector for detecting light incidentthereon and generating an electrical signal responsive thereto, mountedadjacent to the light source on the surface of the substrate in anotherof the cavities, and being separated therefrom by the light shieldingbaffle; a waveguide formed over the light source and the light detector,wherein the light source-containing cavity is filled with a transparentepoxy material having the same refractive index as the waveguide, suchthat the light source may be considered to be located “within” thewaveguide; the waveguide having a mean thickness corresponding to a farfield emission point of the light source as determined by the lightsource's position relative to the light shielding baffle, the intrinsicemission profile of the light source, or a combination of the relativeposition and intrinsic emission profile; and an analyte-permeableindicator matrix disposed on an outer surface of the waveguide, thefluorescent matrix containing fluorescent indicator molecules whosefluorescence is attenuated or enhanced by the presence of analyte insaid fluorescent matrix, the preselected and fluorescent indicatormolecule being selected such that the wavelength emitted by the lightsource excites fluorescence in the indicator molecules; wherein thelight detector generates an electrical signal responsive to fluorescentlight incident thereon emitted by said fluorescent indicator molecules.The photodetector cavity is filled with a color-doped material whichacts as a filter to substantially block from said photodetector emissionwavelengths other than desired peak emission wavelengths from theindicator molecules. The fill-in material for both the photodetector andthe light source cavities can be an epoxy or other polymeric material.

BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The invention will be more fully understood with reference to thefollowing detailed description of a preferred embodiment in conjunctionwith the accompanying drawings, which are given by way of illustrationonly and thus are not limitative of the present invention, and wherein:

[0011]FIG. 1A is a top view of an optical sensor device according to oneembodiment of the present invention;

[0012]FIG. 1B is a side view of the optical sensor device of FIG. 1A;

[0013]FIG. 2A is a side view of the optical sensor device of FIGS.1A-1B, illustrating excitation and indicator response fields of view;

[0014]FIG. 2B is an end view of FIG. 2A;

[0015]FIGS. 3A and 3B are side views illustrating the problem ofemission of light noise from a light source of an optical sensor, andthe solution achieved by the present invention, respectively;

[0016]FIG. 4 is a side view illustrating the use of a curved waveguidesurface for an optical sensor according to an alternate embodiment ofthe invention;

[0017] FIGS. 5A-5D are side views illustrating the optimization ofwaveguide thickness for the sensor device according to the presentinvention; and

[0018]FIG. 6 is a graph showing the light emission profile of an LEDlight source suitable for use with the optical sensor device accordingto the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0019]FIGS. 1A and 1B show an embodiment of an optical sensor deviceaccording to the present invention. The device includes a light source,such as LED 101, and a light detector, such as photodiode 102, mountedon a substrate 100. The light source and light detector are encapsulatedby a waveguide 103, the outer surface of which is provided with afluorescence-indicator matrix 105 containing analyte-indicatormolecules. The matrix 105 is disposed on the outer surface of thewaveguide 103 in one of a variety of different ways, such as bydeposition, coating, adhesion, etc. The light source 101 and lightdetector 102 are separated from each other by an internal baffle 104 a,which is part of a baffle layer portion 104 of the substrate 100. Thebaffle portion 104 may be formed either separately from the substrate100 or integrally with formation of the substrate with subsequentetching or masking of the cavities.

[0020] Baffle layer 104 can be formed over the base layer 110 of thesubstrate 100 to define a number of cavities into which the light sourceand photodetector are placed to be mounted on the substrate. Prior toforming the waveguide layer 103 over the cavities, the light sourcecavity is filled with a transparent epoxy or other polymeric material106, which preferably has substantially the same refractive index as thewaveguide 103. The fill-in material 106 may be, but is not required tobe, the same material used for the waveguide 103.

[0021] The photodetector cavity is filled with a color-doped epoxy orpolymeric material 107, which functions as a filter to block direct orreflected light from the light source 101 from impinging on thephotodetector 102. The color of the material 107 is selected tocorrespond to the peak emission of the indicator molecules.

[0022] Alternately, the photodetector cavity can be filled with thecolor-doped material, and thereafter the light source cavity can befilled simultaneously with the formation of the waveguide layer, suchthat the light source will be embedded within an integrally formedwaveguide layer.

[0023] Additionally, instead of being filled with a clear material, thelight source cavity also may be filled with a color-doped material, thecolor of which is selected to substantially block all wavelengthemissions from the light source other than the desired, peak wavelengthemission.

[0024] As shown in FIGS. 2A and 2B, the configuration of the opticalsensor device according to the invention is based on achievingsubstantially only a direct illumination by the light source 101 ofsubstantially the entire outer surface of the waveguide 103, which isprovided with fluorescence indicator matrix 105, and substantially onlya direct collection on the surface of the photodetector 102 of theresponsive emission from the indicator matrix 105. Internal baffle 104prevents stray illumination of the photodetector 102 by the light source101. The light emission profile geometry of the LED light source isshown in FIG. 6.

[0025] One problem with prior sensor constructs arises from the factthat the light emitted from standard LEDs used as light sources is notat a pure wavelength, but includes a significant amount of lightemission at longer wavelengths, which may reduce the quality of themeasurement signal obtained. For example, a standard blue LED provides a460 nm wavelength emission, but because of various factors, includingfactors involved in the manufacturing process, there is a significantamount (e.g., approximately 0.1% or more of total emission) of lightemission spreading into the red region (e.g., above 600 nm) of thespectrum. The red-doped epoxy material 107 acts as a filter to block theblue wavelengths from being incident on the photodetector 103, butcannot filter out such so-called “red-tail” emissions from the LED lightsource.

[0026] In the case of an oxygen sensor device using ruthenium biphenylphenanthroline as an indicator matrix, the peak emission of suchindicator is 613 nm. Thus, the “red tail” emission of the LEDcontaminates the signal from the indicator. This “red tail” emissioncauses the signal baseline to be elevated and thereby suppresses theuseful readable modulation of fluorescence emission from the indicator.This is shown in FIG. 3A.

[0027] As shown, blue wavelength light emissions 301 (desired) areaccompanied by extraneous, unwanted red wavelength emissions 302, whichcan be reflected by the prior waveguide construct to the detectingsurface of the photodetector 102. According to the direct illuminationconstruct of the present invention, most of the unwanted red wavelengthemissions 302 from the LED light source are not reflected at the surfaceof the waveguide back to the photodetector, but instead pass directlyout of the waveguide, such that substantially only red wavelengthfluorescence emissions 303 in response to excitation from the bluewavelength light waves 301 impinges on the photodetecting surface of thephotodetector 102. According to experimental measurements, baselinenoise is reduced by more than 40 times the level produced by the priorgeometry (e.g., from 23 mV to less than 0.5 mV). Additionally, asdiscussed above, the use of a blue-doped fill-in material in the lightsource cavity can aid in reducing “red-tail” emissions from the lightsource.

[0028] The simplest and most efficient configuration of the opticalsensor device according to the invention is to have a flat surface forthe waveguide, as shown in FIGS. 1A-1B, and 2A-2B. It also is possibleto have a curved surface, as shown at in FIG. 4. Additionally, it ispossible to have other surface geometries such as a sawtooth, gable, orinverse surface pattern, in order to increase surface area and therebyincrease the amount of indicator available for analyte interaction.

[0029] With the prior designs, it was thought that the curved arc of thewaveguide played a role in focusing of the signal light onto thephotodetector. To the contrary, internal reflectance or focusing are notsignificant phenomena according to the design of the present invention.As shown in FIG. 4, the focal point 402 of the arc has no relationshipto the detector 102, and in fact is completely outside of the sensordevice altogether.

[0030] Experimental observations and measurements have confirmed thatthe predominant amount of indicator light is produced in response toonly direct illumination from the light source, as opposed to internallyreflected light.

[0031] FIGS. 5A-5D illustrate a number of different waveguide thicknessoptimizations in light of the discovery that reflectance is not a majorcontributor to signal strength. As shown, various waveguide thicknesseswere fabricated, where the thickness is characterized as a proportion ofthe distance from the LED light source to the intersection of the farfield emission point X of the LED light source with the waveguidesurface. For each thickness, signal strength was measured at a fixed LEDcurrent and amplifier gain. As illustrated, for a waveguide thickness ofX/3, a signal of approximately 5 mV was produced; at 2X/3, a signal ofapproximately 20 mV was produced; at X, a signal of approximately 50 mVwas produced; and at 4X/3, a signal of approximately 40 mV was produced.From these results, it can be seen that the peak signal strength isobtained when the thickness of the waveguide is set equal to X; in otherwords, where the far field emission point of the LED light sourcecoincides with the corner of the waveguide. This may be achieved byappropriate relative positioning between the light source and thebaffle, by selection of a light source with a particular intrinsiceemission profile geometry, or by a combination of these factors.

[0032] Where the surface of the waveguide is made other than flat inorder to obtain an increased surface area, the thickness X is equal tothe mean height of the surface pattern as measured from the lowersurface of the waveguide.

[0033] The optical sensor device according to the invention also may beconfigured as a dual or multi-detector, with photodetectors mounted oneither side of the LED, and different indicator matrices disposed overeach respective photodetector, such that the same excitation wavelengthof the LED may excite different fluorescence wavelengths in eachindicator matrix. Alternatively, multiple LEDs may be used, wherein eachLED emits a different excitation wavelength causing a differentfluorescence wavelength response.

[0034] Further, while refractive index matching has been describedaccording to one preferred embodiment of the invention, it also ispossible to select different refractive indices for each of the lightsource fill-in material, the waveguide material, and the photodetectorfill-in material. It is known that light naturally travels from a mediumhaving a lower refractive index to a medium having a higher refractiveindex.

[0035] Accordingly, since it is desired for excitation light to travelfrom the light source to the indicator matrix disposed on the waveguidesurface, and for fluorescence light emission to travel from theindicator matrix to the photodetector, an alternate embodiment of theinvention would provide successively higher indices of refraction forthe light source fill-in material, the waveguide material, and thephotodetector fill-in material.

[0036] The invention having been thus described, it will be apparent tothose skilled in the art that the same may be varied in many wayswithout departing from the spirit and scope of the invention. Forexample, while the invention has been described with reference to afluorescence sensor device for purposes of illustration, the principlesof the invention may be applied to an optical sensor device usingdetection phenomena other than fluorescence. Any and all suchmodifications are intended to be encompassed by the following claims.

What is claimed is:
 1. An optical sensor device for determining thepresence or concentration of an analyte, comprising: a substrate; alight source for emitting light primarily of a preselected wavelengthupon energization, mounted on a surface of said substrate; a lightdetector for detecting light incident thereon and generating anelectrical signal responsive thereto, mounted on said surface adjacentto said light source, and being separated therefrom by a light shieldingbaffle; a waveguide formed over said light source and said lightdetector; said waveguide having a mean thickness corresponding to a farfield emission point of said light source; and an analyte-permeableindicator matrix disposed on an outer surface of said waveguide, saidindicator matrix containing light-emitting indicator molecules whoselight emission is attenuated or enhanced by the presence of analyte insaid matrix, said indicator molecule being selected such that thewavelength emitted by the light source excites light emission in theindicator molecules; wherein said light detector generates an electricalsignal responsive to light incident thereon emitted by said indicatormolecules.
 2. An optical sensor device according to claim 1, whereinsaid outer surface of said waveguide is substantially flat, and thethickness of said waveguide corresponds to said far field emission pointof said light source.
 3. An optical sensor device according to claim 1,wherein said outer surface of said waveguide is in a curved arcconfiguration.
 4. An optical sensor device according to claim 3, whereina focal point of said curved arc is outside of said sensing device. 5.An optical sensor device according to claim 1, wherein undesiredadditional wavelengths emitted by said light source are caused to passout of said waveguide without being substantially reflected thereby. 6.An optical sensor device according to claim 1, wherein said sensingdevice is used to detect at least two different analytes.
 7. An opticalsensor device according to claim 1, wherein said analyte-permeableindicator matrix is illuminated substantially solely by directillumination from said light source.
 8. An optical sensor deviceaccording to claim 1, wherein said light detector collects substantiallysolely direct fluorescence illumination from said indicator matrix. 9.An optical sensor device according to claim 1, wherein said light sourceis an LED.
 10. An optical sensor device according to claim 1, whereinsaid light detector is a photodiode.
 11. An optical sensor deviceaccording to claim 1, wherein said light-emitting indicator moleculesare fluorescence molecules.
 12. An optical sensor device according toclaim 1, wherein said baffle defines at least two cavities in which saidlight source and said light detector are located when mounted on saidsubstrate, and said waveguide is formed over said cavities.
 13. Anoptical sensor device according to claim 12, further comprising atransparent fill-in material formed over said light source in the cavityin which said light source is located, wherein said transparent fill-inmaterial has a refractive index that is substantially equal to therefractive index of said waveguide, such that said light source is ineffect mounted within said waveguide.
 14. An optical sensor deviceaccording to claim 12, further comprising a color-doped fill-in materialformed over said light source in the cavity in which said light sourceis located, wherein said color-doped fill-in material has a colorcorresponding to a peak wavelength emission of said light source.
 15. Anoptical sensor device according to claim 12, further comprising acolor-doped fill-in material formed over said photodetector in thecavity in which said photodetector is located, wherein said color-dopedfill-in material functions as a filter to block a predominant wavelengthemitted by said light source from impinging on said photodetector. 16.An optical sensor device according to claim 13, wherein said fill-inmaterial is a polymeric material.
 17. An optical sensor device accordingto claim 14, wherein said fill-in material is a polymeric material. 18.An optical sensor device according to claim 15, wherein said fill-inmaterial is a polymeric material.
 19. An optical sensor device accordingto claim 12, further comprising a fill-in material formed over saidlight source in the cavity in which said light source is located,wherein said fill-in material has a refractive index that is lower thanthe refractive index of said waveguide.
 20. An optical sensor deviceaccording to claim 15, wherein said color-doped fill-in material has arefractive index that is higher than the refractive index of saidwaveguide.